U.S. flag

An official website of the United States government

NM_003000.3(SDHB):c.635T>A (p.Leu212His) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 25, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004033618.1

Allele description [Variation Report for NM_003000.3(SDHB):c.635T>A (p.Leu212His)]

NM_003000.3(SDHB):c.635T>A (p.Leu212His)

Gene:
SDHB:succinate dehydrogenase complex iron sulfur subunit B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.13
Genomic location:
Preferred name:
NM_003000.3(SDHB):c.635T>A (p.Leu212His)
HGVS:
  • NC_000001.11:g.17023980A>T
  • NG_012340.1:g.35191T>A
  • NM_003000.3:c.635T>AMANE SELECT
  • NP_002991.2:p.Leu212His
  • LRG_316t1:c.635T>A
  • LRG_316:g.35191T>A
  • NC_000001.10:g.17350475A>T
  • NM_003000.2:c.635T>A
Protein change:
L212H
Links:
dbSNP: rs1307247907
NCBI 1000 Genomes Browser:
rs1307247907
Molecular consequence:
  • NM_003000.3:c.635T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005019679Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Sep 25, 2023) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV005019679.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.L212H variant (also known as c.635T>A), located in coding exon 6 of the SDHB gene, results from a T to A substitution at nucleotide position 635. The leucine at codon 212 is replaced by histidine, an amino acid with similar properties. Based on internal structural analysis, L212H is deleterious. The variant is moderately destabilizing to the local structure and is more destabilizing than several nearby pathogenic variants (Ambry internal data). Another alteration at the same codon, p.L212F (c.634C>T), has been an individual with recurrent paragangliomas, whose tumor showed absent SDHB on immunohistochemistry (Internal Ambry data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024